28 June 2017

This paper examines how governments on both sides of the Atlantic are establishing frameworks that attempt to govern the commercial uses of data. It covers areas such as data analytics driving productivity and growth, the 'industrial internet of things', and the policy context and political forces shaping data rules in the US and Europe.

Invitation Only Research Event

Event participants

Diane Coyle, Professor, University of Manchester; Founder and Managing Director, Enlightenment Economics

Yi Zhang
Sep 1, 2005; 4:1240-1250
Research

MS Brown
Jul 1, 1980; 21:505-517
Reviews

Invitation Only Research Event

Event participants

Rodrigo Malmierca, Minister for Foreign Trade and Investment, Cuba
Chair: Dr Christopher Sabatini, Senior Research Fellow for Latin America, Chatham House; Lecturer, Columbia University, School of International and Public Affairs

Digital technology was not invented to tackle inequality, and there is even a risk that it could widen existing economic and social disparities. But, as the case of China illustrates, new platforms also offer many possible ways to narrow the opportunity gap.

Growth at any cost is, well, costing us — and we can’t rely on the marketplace to solve the earth’s problems.

What happens when a service you shared your personal data with is acquired by a giant corporation?

David Murray-Hundley, the Grumpy Entrepreneur, shares his six pieces of advice for founders of fast growing companies to help maintain control

A. Seesanea and I. E. Verbitsky
St. Petersburg Math. J. 31 (2020), 557-572.
Abstract, references and article information

Claude Cibils, Marcelo Lanzilotta, Eduardo N. Marcos and Andrea Solotar
Proc. Amer. Math. Soc. 148 (2020), 2421-2432.
Abstract, references and article information

How to optimise your website, increase conversions and monetise your online offering

A group of technologists has led crowdsourcing efforts to create a single repository of information for specialists fighting the Coronavirus outbreak. Techworld speaks with founder Edward Saperia to hear more about how collaboration tools can help the efforts

The digital challenger bank is now the most switched to bank in the UK as Nationwide Building Society loses its long-held top spot

Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed in PGAM5-KO BAT, even under unstressed conditions, raising the possibility that PGAM5 deficiency stimulates lipid consumption. However, the mechanism underlying this observation is undetermined. Here, using an array of biochemical approaches, including quantitative RT-PCR, immunoblotting, and oxygen consumption assays, we show that PGAM5 negatively regulates energy expenditure in brown adipocytes. We found that PGAM5-KO brown adipocytes have an enhanced oxygen consumption rate and increased expression of uncoupling protein 1 (UCP1), a protein that increases energy consumption in the mitochondria. Mechanistically, we found that PGAM5 phosphatase activity and intramembrane cleavage are required for suppression of UCP1 activity. Furthermore, utilizing a genome-wide siRNA screen in HeLa cells to search for regulators of PGAM5 cleavage, we identified a set of candidate genes, including phosphatidylserine decarboxylase (PISD), which catalyzes the formation of phosphatidylethanolamine at the mitochondrial membrane. Taken together, these results indicate that PGAM5 suppresses mitochondrial energy expenditure by down-regulating UCP1 expression in brown adipocytes and that its phosphatase activity and intramembrane cleavage are required for UCP1 suppression.

There aren’t a ton of synonyms for the word “hypocrisy.” I’ve become aware of this problem ever since I began writing about the Tara Reade–Joe Biden situation. I keep gravitating towards phrases such as “despicable hypocrisy,” or “partisan hypocrisy,” or “unconscionable hypocrisy,” but you can only go to the well so often. Really, though, I’m not sure how else to describe the actions of someone like Senator Dianne Feinstein.You might recall that it was Feinstein, the ranking member of the Judiciary Committee, who withheld Christine Blasey Ford's allegation of sexual misconduct against Supreme Court nominee Brett Kavanaugh from the Senate so that it could not be properly vetted, in a last-ditch effort to sink the nomination.Feinstein knew that Ford's credibility was brittle -- the alleged victim could not tell us where or when the attack occurred, hadn’t mentioned Kavanugh’s name to anyone for over 30 years, and offered nothing approaching a contemporaneous witness.At first, Feinstein did not want to provide Ford’s name, or a place or time of the alleged attack, or allow the accused to see any evidence against him, denying him the ability to answer the charges.Henceforth this brand of justice could be referred to as “The Joe Biden Standard,” since it’s exactly the kind of show trial the presumptive Democratic nominee promises college kids via Title IX rules.When finally asked about Reade yesterday, Feinstein responded: “And I don’t know this person at all who has made the allegations. She came out of nowhere. Where has she been all these years? He was vice president.”To put this in perspective, when Ford came forward “out of nowhere,” Feinstein said: “Victims must be able to come forward only when they are ready.”What’s changed?During the Kavanaugh hearings Feinstein noted that “sharing an experience involving sexual assault — particularly when it involves a politically connected man with influence, authority and power — is extraordinarily difficult.”Is Biden not a politically connected man with influence, authority, and power? Feinstein is now arguing the opposite: She is saying we should dismiss Reade’s allegations because she failed to come forward against a powerful man earlier.But to answer Feinstein’s question about what Reade has been “up to” the past 27 years: Well, she’s been telling people that Biden had engaged in sexual misconduct. She relayed her story to her former neighbor, her brother, her former co-worker, and at least two other friends. It is also likely that her mother called Larry King Live asking for advice for her daughter the year of the alleged attack.Yesterday a document uncovered by local journalists in California -- somehow missed by Barack Obama’s crack vetting team -- shows Reade’s ex-husband bolstering her claim in 1996 divorce proceedings: “On several occasions [Reade] related a problem that she was having at work regarding sexual harassment, in U.S. Senator Joe Biden's office.”The reaction to the divorce papers has been extraordinary. Biden defenders argue that because Reade alleged “sexual harassment” -- a catch-all term used in the 1990s when men were getting away with despicable behavior far more often -- it proves her story has changed. Biden, through his deputy campaign manager Kate Bedingfield, alleges that “more and more inconsistencies” come up every day.Even if Reade didn't tell everyone everything that allegedly happened every time she mentioned the incident, that doesn’t definitively prove anything. If it did, none of us would have ever heard the name Christine Blasey Ford.Indeed, at time of Ford’s evolving story, there was a slew of journalists taking deep dives into the unreliability of memory and trauma and complexities of relaying assault allegations. I assume that science hasn’t changed in two years.Let’s also not forget that, despite Ford’s inconsistencies, Biden still argued that Kavanaugh should be presumed guilty. Why shouldn’t he?It is also quite amazing to see Biden’s defenders implicitly contending that Reade is only credibly claiming that she was sexually harassed for nearly 30 years, so her story must be politically motivated.Even if we concede that Reade is a wily Sanders operative or Putin stooge, what political motive could Reade possibly have had back in 1993 -- after working for Biden -- to smear the senator? What motive did she have to repeat that story to her family before Sanders was a candidate or Putin was running Russia?By the way, liberals have never argued that political motivations should be disqualifying. Ford came forward, by her own admission, because she did not believe the man who had allegedly assaulted her in high school should be given a seat on highest court in the land. Reade says she doesn’t want a man who allegedly assaulted her -- when he was in his 50s -- to hold the most powerful office in the world.Feinstein, of course, isn’t the only one to engage in this kind of transparent double standard. When asked about Reade, the idealist Alexandria Ocasio-Cortez, said, “I’m not sure. Frankly, this is a messy moment, and I think we need to acknowledge that -- that it is not clear-cut.”Where was all this hand-wringing and caution over the messiness of sexual-assault claims when nearly every Democrat and all their allies in the press were spreading Julie Swetnick’s alleged “gang rape” piece? Nowhere.AOC, whose position on Biden has evolved, invited Ana Maria Archila, the women who had famously cornered a weak-kneed senator Jeff Flake in an elevator and yelled at him about Kavanaugh, to the 2019 State of the Union address. Archila now says, “I feel very trapped.”I bet.People point out that there are numerous sexual-misconduct allegations leveled at Donald Trump. Indeed. If they haven’t yet, news outlets should scrutinize and investigate the credibility of those allegations, as they did for Biden but not for Kavanaugh. But it’s important to remember that Trump accuser E. Jean Carroll was given immediate and widespread coverage on cable news, while Reade reportedly wasn’t asked to tell her story by any major network -- save Fox News -- until this week.Of course, most Biden defenders are being purposely obtuse about the debate -- Mona Charen’s recent column is an excellent example. The problem isn’t that Biden is being treated unjustly, or that he should be treated unjustly; it’s that he is being treated justly by the same people who treat others unjustly. Democrats have yet to explain why Biden is afforded every benefit of the doubt but not Kavanaugh, and not millions of college students.Public figures such as Biden have every right to demand fair hearings and due process. Voters have every right to judge the credibility of both accuser and accused. Many women are victims. Many women are victims who are powerless to prove it. And some women are frauds. You can’t keep demanding that our political system adjudicate similar incidents under two completely differ set of rules. It’s untenable.

18 February 2019

Samuel W Entwisle
Apr 6, 2020; 0:RA120.001946v2-mcp.RA120.001946
Research

Recently-adopted techniques advance LockBit to a major ransomware player...for now.

Insulin-like growth factors (IGFs), specifically IGF1 and IGF2, promote glucose metabolism, with their availability regulated by IGF-binding proteins (IGFBPs). We hypothesized that IGF1 and IGF2 levels, or their bioavailability, are reduced during type 1 diabetes development. Total serum IGF1, IGF2, and IGFBP1–7 levels were measured in an age-matched, cross-sectional cohort at varying stages of progression to type 1 diabetes. IGF1 and IGF2 levels were significantly lower in autoantibody (AAb)⁺ compared with AAb^– relatives of subjects with type 1 diabetes. Most high-affinity IGFBPs were unchanged in individuals with pre–type 1 diabetes, suggesting that total IGF levels may reflect bioactivity. We also measured serum IGFs from a cohort of fasted subjects with type 1 diabetes. IGF1 levels significantly decreased with disease duration, in parallel with declining β-cell function. Additionally, plasma IGF levels were assessed in an AAb⁺ cohort monthly for a year. IGF1 and IGF2 showed longitudinal stability in single AAb⁺ subjects, but IGF1 levels decreased over time in subjects with multiple AAb and those who progressed to type 1 diabetes, particularly postdiagnosis. In sum, IGFs are dysregulated both before and after the clinical diagnosis of type 1 diabetes and may serve as novel biomarkers to improve disease prediction.

Methods that provide rapid access to radiolabeled antibodies are vital in the development of diagnostic and radiotherapeutic agents for positron emission tomography (PET) or radioimmunotherapy. The human hepatocyte growth factor receptor (c-MET) signaling pathway is dysregulated in a number of malignancies including gastric cancer, and is an important biomarker in drug discovery. Here, we used a photoradiochemical approach to produce ⁸⁹Zr-radiolabeled onartuzumab (a monovalent, anti-human c-MET antibody), starting directly from the fully formulated drug (MetMAb). Methods: Simultaneous ⁸⁹Zr-radiolabeling and protein conjugation was performed in one-pot reactions containing ⁸⁹Zr-oxalate, the photoactive chelate DFO-aryl azide (DFO-ArN3) and MetMAb to give ⁸⁹ZrDFO-azepin-onartuzumab. As a control, ⁸⁹ZrDFO-Bn-NCS-onartuzumab was prepared via a conventional two-step process using pre-purified onartuzumab and DFO-Bn-NCS. Radiotracers were purified by using size-exclusion methods and evaluated by radiochromatography. Radiochemical stability was studied in human serum and immunoreactivity was determined by cellular binding assays using MKN-45 gastric carcinoma cells. PET imaging at multiple time points (0–72 h) was performed in female athymic nude mice bearing subcutaneous MKN-45 xenografts. Biodistribution experiments were performed after the final image. Tumor specificity of ⁸⁹ZrDFO-azepin-onartuzumab was assessed by competitive inhibition (blocking) studies. Results: Initial photoradiosynthesis experiments produced ⁸⁹ZrDFO-azepin-onartuzumab in <15 min. with an isolated decay-corrected radiochemical yield (RCY) of 24.8%, a radiochemical purity (RCP) ~90% and a molar activity (Am) of ~1.5 MBq nmol^-1. Reaction optimization improved the radiochemical conversion (RCC) of ⁸⁹ZrDFO-azepin-onartuzumab to 56.9±4.1% (n = 3), with isolated RCYs of 41.2±10.6% (n = 3), and RCPs >90%. Conventional methods produced ⁸⁹ZrDFO-Bn-NCS-onartuzumab with isolated RCY >97%, RCP >97% and Am ~14.0 MBq nmol^-1. Both radiotracers were immunoreactive and stable in human serum. PET imaging and biodistribution studies showed high tumor uptake for both radiotracers. By 72 h, tumor and liver uptake reached 15.37±5.21 %ID g^-1, 6.56±4.03 %ID g^-1, respectively for ⁸⁹ZrDFO-azepin-onartuzumab (n = 4), and 21.38±11.57 %ID g^-1 and 18.84±6.03 %ID g^-1 for ⁸⁹ZrDFO-Bn-NCS-onartuzumab (n = 4). Blocking experiments gave a statistically significant reduction in tumor uptake (6.34±0.47 %ID g^-1) of ⁸⁹ZrDFO-azepin-onartuzumab (n = 4). Conclusion: Experiments demonstrate that photoradiosynthesis is a viable alternative approach for producing ⁸⁹Zr-radiolabeled antibodies direct in protein formulation buffer which reduces protein aggregation and liver uptake.

Invitation Only Research Event

Event participants

Abebe Aemro Selassie, Director, African Department, International Monetary Fund
Chair: Elizabeth Donnelly, Deputy Head and Research Fellow, Africa Programme, Chatham House

3 October 2019

The Chatham House Africa Programme designed the Sudan Stakeholder Dialogues series to help identify the factors that have led to the current economic crisis, the immediate steps that need to be taken to avert collapse and stabilize the economy, and the longer-term structural reforms required to set Sudan on the path to recovery. The project is funded by Humanity United.

10 October 2019

This briefing note is the result of a collaborative research process with the Zimbabwean private sector, government representatives, industry organizations and experts, drawing on best practice and senior-level insights to identify policy options for long-term economic revival and expansion in Zimbabwe, and pathways for inclusive development.

Research Event

Event participants

Hon Bruno Nabagné Kone, Minister of Construction, Housing and Urban Planning, Republic of Côte d'Ivoire

Research Event

Event participants

Paul Mashatile, Treasurer General, African National Congress (ANC)

Glycosylation is a common modification of proteins and critical for a wide range of biological processes. Differences in protein glycosylation between sexes have already been observed in humans, nematodes and trematodes, and have recently also been reported in the rice pest insect Nilaparvata lugens. Although protein N-glycosylation in insects is nowadays of high interest because of its potential for exploitation in pest control strategies, the functionality of differential N-glycosylation between sexes is yet unknown. In this study, therefore, the occurrence and role of sex-related protein N-glycosylation in insects were examined. A comprehensive investigation of the N-glycosylation sites from the adult stages of N. lugens was conducted, allowing a qualitative and quantitative comparison between sexes at the glycopeptide level. N-glycopeptide enrichment via lectin capturing using the high mannose/paucimannose-binding lectin Concanavalin A, or the Rhizoctonia solani agglutinin which interacts with complex N-glycans, resulted in the identification of over 1300 N-glycosylation sites derived from over 600 glycoproteins. Comparison of these N-glycopeptides revealed striking differences in protein N-glycosylation between sexes. Male- and female-specific N-glycosylation sites were identified, and some of these sex-specific N-glycosylation sites were shown to be derived from proteins with a putative role in insect reproduction. In addition, differential glycan composition between males and females was observed for proteins shared across sexes. Both lectin blotting experiments as well as transcript expression analyses with complete insects and insect tissues confirmed the observed differences in N-glycosylation of proteins between sexes. In conclusion, this study provides further evidence for protein N-glycosylation to be sex-related in insects. Furthermore, original data on N-glycosylation sites of N. lugens adults are presented, providing novel insights into planthopper's biology and information for future biological pest control strategies.

Accumulating evidence suggests that brown adipose tissue (BAT) is a potential therapeutic target for managing obesity and related diseases. PGAM family member 5, mitochondrial serine/threonine protein phosphatase (PGAM5), is a protein phosphatase that resides in the mitochondria and regulates many biological processes, including cell death, mitophagy, and immune responses. Because BAT is a mitochondria-rich tissue, we have hypothesized that PGAM5 has a physiological function in BAT. We previously reported that PGAM5-knockout (KO) mice are resistant to severe metabolic stress. Importantly, lipid accumulation is suppressed in PGAM5-KO BAT, even under unstressed conditions, raising the possibility that PGAM5 deficiency stimulates lipid consumption. However, the mechanism underlying this observation is undetermined. Here, using an array of biochemical approaches, including quantitative RT-PCR, immunoblotting, and oxygen consumption assays, we show that PGAM5 negatively regulates energy expenditure in brown adipocytes. We found that PGAM5-KO brown adipocytes have an enhanced oxygen consumption rate and increased expression of uncoupling protein 1 (UCP1), a protein that increases energy consumption in the mitochondria. Mechanistically, we found that PGAM5 phosphatase activity and intramembrane cleavage are required for suppression of UCP1 activity. Furthermore, utilizing a genome-wide siRNA screen in HeLa cells to search for regulators of PGAM5 cleavage, we identified a set of candidate genes, including phosphatidylserine decarboxylase (PISD), which catalyzes the formation of phosphatidylethanolamine at the mitochondrial membrane. Taken together, these results indicate that PGAM5 suppresses mitochondrial energy expenditure by down-regulating UCP1 expression in brown adipocytes and that its phosphatase activity and intramembrane cleavage are required for UCP1 suppression.